File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Bradykinin and high glucose promote renal tubular inflammation

TitleBradykinin and high glucose promote renal tubular inflammation
Authors
KeywordsBradykinin
Chemokines
Diabetic nephropathy
High glucose
Kallirein
Issue Date2010
PublisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/
Citation
Nephrology Dialysis Transplantation, 2010, v. 25 n. 3, p. 698-710 How to Cite?
Abstract
Background. The role of the kallikrein-kinin system in diabetic nephropathy remains controversial.Methods and Results. High-glucose (HG) super-induced interleukin (IL)-6, CCL-2, transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF) and B2K receptor (B2KR) mRNA in cultured proximal tubular epithelial cells (PTEC), whereas bradykinin (BK) upregulated IL-6, CCL-2 and TGF-β mRNA. HG activated mitogen-activated protein kinase (MAPK) p42/p44 and protein kinase C (PKC) signals, whereas BK only activated MAPK. Tubular expression of these mediators and tissue kallikrein 1 (KLK1) was confirmed in human diabetic kidney biopsies. Inhibition of MAPK p42/p44 by PD98059 partially reduced HG and BK induction of IL-6, CCL-2 and TGF-β, whereas inhibition of PKC by staurosporine partially reduced HG-but not BK-induced overexpression of these cytokines and that of VEGF. Staurosporine and PD98059 synergistically reduced the effect of HG on IL-6, CCL-2 and TGF-β expression. The B2KR blocker, icatibant, downregulated BK-and HG-induced MAPK p42/p44 but not HG-induced PKC activation and partially reduced both HG-and BK-induced IL-6, CCL-2 and TGF-β secretion. HG stimulated expression of KLK1 and low-molecular-weight kininogen (LMWK) and its downstream effects were attenuated by aprotinin (tissue kallikrein inhibitor). The peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, attenuated HG-induced PKC but not HG-or BK-induced MAPK p42/44 activation and reduced HG-stimulated VEGF, along with IL-6, CCL-2 and TGF-β secretion. Rosiglitazone plus icatibant further reduced these effects of HG.Conclusions. In conclusion, HG stimulates tubular proinflammatory, profibrotic and angiogenic signals, which is partly mediated through BK via MAPK signalling and partly through PKC independent of BK. The potential therapeutic role of complementary B2KR blockade and PPAR-γ activation deserves clinical investigation.
Persistent Identifierhttp://hdl.handle.net/10722/65486
ISSN
2013 Impact Factor: 3.488
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 7764/07M
Funding Information:

This work was supported by the Research Grants Council (General Research Fund ref HKU 7764/07M) of Hong Kong. Part of the data contained in this study was presented in abstract form at the American Society of Nephrology Annual Meeting and Scientific Exposition, November 6-9, 2008, Philadelphia, PA, USA. Icatibant was a kind gift from Sanofi-Aventis Deutschland GmbH. Rosiglitazone was a kind gift from GlaxoSmithKline (Compound Management Division, Stevenage, Herts, UK).

References

 

DC FieldValueLanguage
dc.contributor.authorTang, SCWen_HK
dc.contributor.authorChan, LYYen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorCheng, ASen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2010-08-12T04:36:57Z-
dc.date.available2010-08-12T04:36:57Z-
dc.date.issued2010en_HK
dc.identifier.citationNephrology Dialysis Transplantation, 2010, v. 25 n. 3, p. 698-710en_HK
dc.identifier.issn0931-0509en_HK
dc.identifier.urihttp://hdl.handle.net/10722/65486-
dc.description.abstractBackground. The role of the kallikrein-kinin system in diabetic nephropathy remains controversial.Methods and Results. High-glucose (HG) super-induced interleukin (IL)-6, CCL-2, transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF) and B2K receptor (B2KR) mRNA in cultured proximal tubular epithelial cells (PTEC), whereas bradykinin (BK) upregulated IL-6, CCL-2 and TGF-β mRNA. HG activated mitogen-activated protein kinase (MAPK) p42/p44 and protein kinase C (PKC) signals, whereas BK only activated MAPK. Tubular expression of these mediators and tissue kallikrein 1 (KLK1) was confirmed in human diabetic kidney biopsies. Inhibition of MAPK p42/p44 by PD98059 partially reduced HG and BK induction of IL-6, CCL-2 and TGF-β, whereas inhibition of PKC by staurosporine partially reduced HG-but not BK-induced overexpression of these cytokines and that of VEGF. Staurosporine and PD98059 synergistically reduced the effect of HG on IL-6, CCL-2 and TGF-β expression. The B2KR blocker, icatibant, downregulated BK-and HG-induced MAPK p42/p44 but not HG-induced PKC activation and partially reduced both HG-and BK-induced IL-6, CCL-2 and TGF-β secretion. HG stimulated expression of KLK1 and low-molecular-weight kininogen (LMWK) and its downstream effects were attenuated by aprotinin (tissue kallikrein inhibitor). The peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, attenuated HG-induced PKC but not HG-or BK-induced MAPK p42/44 activation and reduced HG-stimulated VEGF, along with IL-6, CCL-2 and TGF-β secretion. Rosiglitazone plus icatibant further reduced these effects of HG.Conclusions. In conclusion, HG stimulates tubular proinflammatory, profibrotic and angiogenic signals, which is partly mediated through BK via MAPK signalling and partly through PKC independent of BK. The potential therapeutic role of complementary B2KR blockade and PPAR-γ activation deserves clinical investigation.en_HK
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/en_HK
dc.relation.ispartofNephrology Dialysis Transplantationen_HK
dc.rightsNephrology, Dialysis, Transplantation. Copyright © Oxford University Press.-
dc.rightsThis is a pre-copy-editing, author-produced PDF of an article accepted for publication in Nephrology, Dialysis, Transplantation following peer review.-
dc.subjectBradykininen_HK
dc.subjectChemokinesen_HK
dc.subjectDiabetic nephropathyen_HK
dc.subjectHigh glucoseen_HK
dc.subjectKallireinen_HK
dc.subject.meshBradykinin - physiology-
dc.subject.meshDiabetic Nephropathies - pathology - physiopathology-
dc.subject.meshGlucose - physiology-
dc.subject.meshHyperglycemia - physiopathology-
dc.subject.meshKidney Tubules, Proximal - pathology - physiopathology-
dc.titleBradykinin and high glucose promote renal tubular inflammationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0931-0509&volume=25&issue=3&spage=698&epage=710&date=2010&atitle=Bradykinin+and+high+glucose+promote+renal+tubular+inflammation-
dc.identifier.emailTang, SCW: scwtang@hku.hken_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailChan, KW: hrmtckw@hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityTang, SCW=rp00480en_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/ndt/gfp599en_HK
dc.identifier.pmid19923143en_HK
dc.identifier.scopuseid_2-s2.0-77649226697en_HK
dc.identifier.hkuros174356-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77649226697&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue3en_HK
dc.identifier.spage698en_HK
dc.identifier.epage710en_HK
dc.identifier.isiWOS:000274987800012-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTang, SCW=7403437082en_HK
dc.identifier.scopusauthoridChan, LYY=55182644100en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridCheng, AS=21733421700en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridLan, HY=24544799000en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.citeulike6185871-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats